BERKELEY, CA (UroToday.com) - In 1996, the Lancet published a commentary regarding the deficit of high quality surgical research, noting that almost half (46%) of papers reported data from case series while only 7% of studies had results from randomized clinical trials.[1] Despite the attention garnered at that time, and a push within the surgical community to demand higher quality data, a similar analysis a decade later reported that the percentage of surgical research articles generating data from randomized trials was only 10%.[2] This begs the question: why are randomized clinical trials in surgery so difficult (and rarely performed)? The challenges to clinical trials in surgery are multiple and unique; many were considered and arose in the course of development and conduct of our study, which investigated whether the early removal of a urethral catheter with suprapubic tube (SPT) drainage following robot-assisted laparoscopic prostatectomy (RALP) would improve postoperative pain compared with traditional urethral catheter drainage alone.[3] We will briefly outline key challenges and our experience below:
- Blinding and crossover: Blinding is always difficult in surgical treatments, especially when there is no sham/placebo arm and patients simply have to look down at their incision to determine their randomization assignment. However, the intervention was assigned at the end of the surgical procedure, minimizing potential performance bias by the surgeon in regards to operative time, blood loss, etc.
- Preference for specific study arm: In a city with 5 academic urology programs and many high-quality private hospitals, our patients often had multiple prior opinions for their prostate cancer prior to selection of our institution for surgery. Many came specifically because they heard that a “catheter-less” RALP was being performed and expressed desire to specifically be assigned that intervention. We elected, during the study period, to only offer SPT placement as part of the trial; therefore, in men who elected not to participate in the study, the standard urethral catheter alone was used for post-operative drainage. Given the very few centers, nationwide, performing concomitant SPT placement at the time of RALP, we fortunately did not have issues with accrual secondary to patients seeking out other centers based on their treatment preference.
- Equipoise: This ethical issue addresses the question regarding whether there is truly uncertainly regarding the comparative merits of the two study interventions. Prior observational data from Menon and colleagues[4] demonstrated a benefit in post-operative pain, and our own pre-trial experience in approximately 200 patients suggested the same. However, given that the primary outcome was pain and the additional interventional step of placing the SPT added cost and time to the procedure, we believed that formal study of the differences between the two study arms was appropriate.
- Endpoint: Our study was powered based on the published results from the initial study from the VUI group. We sought a relatively modest one-point improvement on a validated pain measurement tool, which we thought was a meaningful clinical endpoint and was based on review of other surgical trials using similar pain score differences. As such, our study was designed for slightly over 100 patients and an interim analysis (which led to early closure of the study) was performed at the halfway point for futility or efficacy.
- Learning curve: One of the benefits of performing this study at a single institution was that surgical experience with both RALP and robotic SPT placement was controlled. However, the level of expertise of the two surgeons (> 2000 procedures performed) and the preliminary non-randomized experience aided in the performance of the study with minimal complications.
It is important to note that the RCT is not the only valid method to compare treatments, and for many surgical questions, a RCT may be impossible to conduct and complete without bias.[5] Small, poorly conducted trials are more likely to occur when trials are difficult to conduct and these may be particularly misleading as the study design may confer “unwarranted credibility.”[6] In the end, however, an appropriately performed RCT is much stronger than an observational study, regardless of the number of patients included. We elected to conduct a randomized clinical trial to diffuse criticism that our use of the SPT was a “gimmick” or “marketing tool.” We found no difference between the two treatment groups in regards to post-operative pain on futility analysis and ended our study. In truth, we were surprised that our study demonstrated no difference. In support of our findings, however, we no longer routinely perform SPT following RALP.
References:
- Horton R. Surgical research or comic opera: questions, but few answers. Lancet 1996; 347: 984-5.
- Gelijns AC, Ascheim DD, Parides MK, et al. Randomized trials in surgery. Surgery 2009; 145: 581-7.
- Prasad, S.M., Large, M.C., Patel, A.R. et al.: Randomized controlled trial of early removal of urethral catheter with suprapubic tube drainage versus urethral catheter drainage alone following robot-assisted laparoscopic radical prostatectomy. J Urol 2014 [epub ahead of print]
- Krane LS, Bhandari M, Peabody JO et al. Impact of percutaneous suprapubic tube drainage on patient discomfort after radical prostatectomy. European Urology 2009; 56: 325-30.
- Jacobs WCH, Kruty MC, and Oner FC. Recruiting patients into randomized clinical trials in surgery. Br J Surg 2012; 99: 307-8.
- McCulloch P, Taylor I, Sasako M, et al. Randomised trials in surgery: problems and possible solutions. BMJ 2002; 324: 1448-51.
Written by:
Sandip M. Prasad, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Department of Urology, Medical University of South Carolina, Charleston, South Carolina USA
More Information about Beyond the Abstract